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Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation.

Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation.

期刊: Clinical and translational science 日期: 2026-08-01 PMID: 42572225 DOI: 10.1111/cts.70698 浏览: 8
作者: Pippis CA, Lopez-Medina AI, Chahal CAA, Luzum JA
CA, P., AI, L.M., CAA, C., & JA, L. (2026). Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation.. Clinical and translational science. https://doi.org/10.1111/cts.70698
CA P, AI LM, CAA C, JA L. Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation.. Clinical and translational science. 2026; doi: 10.1111/cts.70698
CA P, AI LM, CAA C, et al. Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation.[J]. Clinical and translational science. 2026. DOI: 10.1111/cts.70698.
@article{ca2026,
  author = {Pippis CA and Lopez-Medina AI and Chahal CAA and Luzum JA},
  title = {Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation.},
  journal = {Clinical and translational science},
  year = {2026},
  doi = {10.1111/cts.70698},
  note = {PMID: 42572225},
}
TY  - JOUR
AU  - Pippis CA
AU  - Lopez-Medina AI
AU  - Chahal CAA
AU  - Luzum JA
TI  - Association of the NOS1AP rs10494366 Genetic Variant With Drug-Induced QT Prolongation.
T2  - Clinical and translational science
PY  - 2026
DO  - 10.1111/cts.70698
AN  - PMID:42572225
ER  - 

摘要

Drug-induced QTc prolongation (diQTP) is a major risk factor for torsades de pointes and sudden cardiac death. This study evaluated whether carriers of the G allele of the NOS1AP rs10494366 T > G variant have greater risk for diQTP when prescribed high-risk QT-prolonging medications. A retrospective case-control analysis was conducted using the Michigan Genomics Initiative (MGI) biobank, linking genotype and electronic health records for 5848 patients of European ancestry prescribed ≥ 1 CredibleMeds high-risk drug for torsades de pointes between 2001 and 2022. QTc was Bazett-corrected, and diQTP was defined as change of > 60 ms from the baseline QTc and/or QTc ≥ 500 ms. Associations between rs10494366 and diQTP were tested using unadjusted and propensity-score-adjusted logistic regression. The minor-allele frequency (G) was 0.36, and genotype frequencies were in Hardy-Weinberg equilibrium (p = 0.07). diQTP occurred in 12.2% of participants. The G allele was not significantly associated with risk of diQTP in either the unadjusted analysis (OR 0.94 [95% CI 0.84-1.05] p = 0.27) or the adjusted analysis (OR 0.94 [95% CI 0.83-1.06] p = 0.30). In this large, real-world cohort of patients with European ancestry, the NOS1AP rs10494366 variant was not significantly associated with the risk of diQTP. These findings suggest that previously observed associations between this variant and baseline QTc may not extend to all drug-induced settings.

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